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PubMed2001

Fibroblast growth factor-2 promotes axon branching of cortical neurons by influencing morphology and behavior of the primary growth cone.

Interstitial branching is an important mechanism for target innervation in the developing CNS. A previous study of cortical neurons in vitro showed that the terminal growth cone pauses and enlarges in regions from which interstitial axon branches later develop (Szebenyi et al., 1998). In the present study, we investigated how target-derived signals affect the morphology and behaviors of growth cones leading to development of axon branches. We used bath and local application of a target-derived growth factor, FGF-2, on embryonic pyramidal neurons from the sensorimotor cortex and used time-lapse digital imaging to monitor effects of FGF-2 on axon branching. Observations of developing neurons over periods of several days showed that bath-applied FGF-2 significantly increased growth cone size and slowed growth cone advance, leading to a threefold increase in axon branching. FGF-2 also had acute effects on growth cone morphology, promoting rapid growth of filopodia within minutes. Application of FGF-2-coated beads promoted local axon branching in close proximity to the beads. Branching was more likely to occur when the FGF-2 bead was on or near the growth cone, suggesting that distal regions of the axon are more responsive to FGF-2 than other regions of the axon shaft. Together, these results show that interstitial axon branches can be induced locally through the action of a target-derived growth factor that preferentially exerts effects on the growth cone. We suggest that, in target regions, growth factors such as FGF-2 and other branching factors may induce formation of collateral axon branches by enhancing the pausing and enlargement of primary growth cones that determine future branch points.

Animals↗
PubMed1992

Responding to acoustic startle during chronic ethanol intoxication and withdrawal.

Ethanol (EtOH) withdrawal is characterized by a hyperexcitable state that includes anxiety, tremor, muscle rigidity and seizures. The present three experiments examined the effects of EtOH dependence and withdrawal on the acoustic startle response, an easily quantifiable measure of behavioral reactivity to exteroceptive stimuli. Two intensities of startle stimuli, 105 and 120 dB pulses, were presented to rats during chronic EtOH exposure and during EtOH withdrawal. Prepulse inhibition, which is a sensitive measure of sensorimotor gating processes associated with filtering sensory stimulation, was also assessed during chronic EtOH exposure and withdrawal. Prepulse inhibition was induced by the presentation of a weak 80 dB acoustic stimulus 100 ms prior to a 120 dB stimulus pulse. After 14 days of EtOH liquid diet administration the magnitude of responses elicited by 105 and 120 dB startle stimuli was less in ethanol-treated subjects during continued EtOH access than in animals fed a control liquid diet. When EtOH liquid diet treatment was continued for an additional 3-day period and animals were tested 8 h after withdrawal from EtOH, withdrawn animals were more reactive to startle stimuli at both intensities than were animals maintained on the EtOH liquid diet. A time-course experiment with repeated startle testing at 4, 8, and 12 h post-EtOH exposure revealed significant increases in responding to the 105 dB startle intensity at 8 h post-EtOH exposure. The ability of animals to respond to a prepulse stimulus was not affected during chronic EtOH treatment, but was reduced during withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed2001

Cortical barrel field ablation and unconditioned whisking kinematics.

The effects of "barrel cortex" ablation upon the biometrics of "exploratory" whisking were examined in three head-fixed rats which had previously sustained unilateral ablation of the left cortical "barrel field" under electrophysiological control. Unconditioned movements of a pair of bilaterally homologous whiskers (C-1, Right, Left) were monitored, optoelectronically, with other whiskers present. Whisking movements on the intact and ablated side were analyzed with respect to kinematics (protraction amplitude and velocity) whisking frequency and phase relationships between whisking movement on the two sides of the face. Histological analysis confirmed complete removal of S-1 "barrel cortex". In normal animals whisking movements have a characteristic rhythm (6-9 Hz), and protractions on the two sides of the face tend to be both synchronous and of very similar amplitudes. In the lesioned animals, whisking frequency was unchanged and whisking movements remained bilaterally synchronous. However, there was a significant difference between the amplitude of Right and Left whisker movements which was evident many months postoperatively. Our results suggest that the deficits in vibrissa-mediated tactile discrimination reported after "barrel" field ablation may reflect an impairment in the animal's ability to modulate whisking parameters on the two sides of the face to meet the functional requirements of a discriminative whisking task. The effects upon whisking amplitude seen after unilateral barrel field ablation are consistent with a model in which the activity of a whisking Central Pattern Generator is modulated by descending inputs to achieve sensorimotor control of whisking movement parameters.

Animals↗
PubMedDate not supplied

[The formation of conditioned reflexes to a complex signal in ontogeny under the conditions of an alternation choice].

Formation of conditioned reflex to simultaneous complex stimulus (light + sound) and its components was studied in alternation task (Go/Go) in kittens aged 1.5-10 months. Low percentage of correct reactions (48-57%) and preference of one of the two reinforced directions were shown in kittens aged 1.5-5 months. Successful learning in alternation task was attained in kittens which began to be trained at the age of 6 months. Extirpation of sensorimotor cortex in the trained animals aged 7 months and older induced a decrease of the level of correct reactions from 75-80% to 20-40% and preference of one direction. The problems of parallel development of interaction between the sensory and motor systems and sensorimotor cortex are discussed.

Acoustic Stimulation↗
PubMed2001

Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat.

The role played by chronic episodic hypoxia (EHYP) in the neurocognitive morbidity of obstructive sleep apnea (OSA) is unknown. Sleep recordings, Morris water maze experiments, and immunohistochemistry for NMDA NR1 glutamate receptor, c-fos protein, and apoptosis [nuclear immunoreactivity for single-stranded DNA and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay] were conducted in EHYP-exposed Sprague Dawley male rats. Exposures consisted of up to14 d in an environmental chamber in which O(2) concentrations were cycled between 10 and 21% every 90 sec or 30 min during 12 hr of daylight. For the remaining 12 hr, EHYP rats breathed room air, while controls spent 14 d in room air. Although EHYP induced significant disruption of sleep architecture during the initial day of exposure, sleep patterns normalized thereafter. Marked increases in apoptosis occurred in the CA1 hippocampal region (sevenfold) and cortex (Cx; eightfold) after 1-2 d of EHYP but not in CA3 and were followed by decreases toward normoxic levels by 14 d. Double labeling for NMDA NR1 and c-fos revealed marked architectural disorganization in CA1 and Cx with increases in c-fos over time. Rats exposed to EHYP displayed significantly longer escape latencies and swim path lengths to escape a hidden platform during 12 training trials given over 2 d. Differences in the performances of EHYP and control rats, although reduced, persisted after 14 d of recovery. We conclude that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions. Furthermore, EHYP impaired performance during acquisition of a cognitive spatial task without affecting sensorimotor function. Such changes may underlie components of the learning and memory impairments found in OSA.

Animals↗
PubMed1976

A comparison of hypothalamically induced biting attack with natural predatory behavior in the cat.

A comparison of biting attack induced by electrical stimulation of the cat hypothalamus with natural feline predatory attack revealed a high degree of similarity between the two behaviors. All major components of natural attack could be elicited by hypothalamic stimulation in cats not showing spontaneous attack, including stalking approach to prey, holding and pinning of the prey with forepaws, biting directed to the head and neck, prey kicking, prey carrying, and prey eating. Differences between natural and elicited attack appeared to be related to the range of completenes of elicited attack, the greater intensity of elicited attack, and the presence of unrelated responses induced by hypothalamic stimulation. Results support the view that hypothalamic stimulation facilitates sensorimotor mechanisms for separate response components, which are highly sensitive to specific stimulus features of the environment and potential goal objects.

Aggression↗
PubMed2001

Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/- BDNF mutant mice.

Deletion of a single copy of the BDNF gene has been shown to affect the nigrostriatal dopaminergic system of young adult BDNF mice. In the present report we evaluated various indices of nigrostriatal dopaminergic function between 9-month-old wild-type (+/+) and heterozygous (+/-) BDNF mutant mice. Performance in a sensorimotor beam walking task was significantly decreased in +/- mice as indicated by increased times required to traverse both a wide (21 mm) and narrow (6 mm) beam. No differences in spontaneous locomotor behavior were observed between the +/+ and +/- mice. Amphetamine-stimulated (5 mg/kg) locomotor behavior was increased to a greater degree in the +/- mice, with the number of movements performed by these mice being significantly greater than their +/+ controls. Corpus striatal dopamine concentrations were significantly greater in the +/- BDNF mice. The absence of any significant differences for dopamine concentrations within the hypothalamus and olfactory bulb of these mice, as well as an absence of any difference in striatal norepinephrine concentrations, suggested a relative specificity of these effects to the corpus striatum. Both the +/- and +/+ mice showed similar reductions in striatal dopamine concentrations in response to a neurotoxic regimen of methamphetamine (20 mg/kg). Collectively these data show increased levels of striatal dopamine concentrations associated with altered behavioral responses involving the nigrostriatal dopaminergic system within the heterozygous BDNF mutant mice.

Animals↗
PubMed1993

Protective effects of SR 57746A in central and peripheral models of neurodegenerative disorders in rodents and primates.

Compounds possessing neurotrophic properties may represent a possible treatment for neurodegenerative disorders such as Alzheimer's disease. SR 57746A, 1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride, is a new compound with neurotrophic activity in a number of in vitro preparations. The neurotrophic effects of this compound have been evaluated in vivo using four distinct rat models of neurodegeneration: transient global ischaemia produced by a four-vessel occlusion; septohippocampal lesion produced by injection of vincristine sulphate into the medial septum; sciatic nerve crushing; and acrylamide-induced peripheral neuropathy. Rats were administered vehicle or 2.5-10 mg/kg p.o. SR 57746A, after initiation of the degenerative process, then once daily for 10 days in the first two models, 16 days in the third and 26 days in the fourth model. Median scores for ischaemia-induced neuronal damage were reduced by 30-40% by SR 57746A treatment in hippocampal CA1, CA2, and CA3 regions, and in the dorsal striatum. Twelve days after intraseptal vincristine administration, there was a marked loss of septohippocampal cholinergic neurons, as indicated by reduced choline acetyltransferase activity in both the septum and hippocampus. SR 57746A dose-dependently reversed this reduction in both areas. These results were confirmed by histoenzymological evaluation of hippocampal acetylcholinesterase content. SR 57746A also reversed the loss of hippocampal choline acetyltransferase induced by intraseptal vincristine in marmosets. Behavioral deficits in these models (exploratory behaviour in the former and short-term social memory in the latter) were also significantly reduced by SR 57746A treatment. In the sciatic crush model, sensorimotor function improved more rapidly in rats treated with 10 mg/kg SR 57746A. In this same model, SR 57746A (10 mg/kg/day) also significantly increased the length of regenerated nerve eight days after the crush, as measured using the pinch test. Finally, SR 57746A retarded the onset, reduced the amplitude and accelerated the recovery of acrylamide-induced peripheral neuropathy. Thus, SR 57746A possesses notable neurotrophic activity in a variety of neurodegenerative models in vivo, suggesting that the compound may possess therapeutic potential for the treatment of neurodegenerative diseases.

Acetylcholinesterase↗
PubMed1998

Kainic acid-induced perirhinal cortical seizures in rats.

Seizures induced in rats by kainic acid microinjection into the perirhinal cortex were studied electrophysiologically and behaviorally and compared with known features of seizures following kainic acid injection into the amygdala. Unlike amygdalar seizures, perirhinal cortical seizures did not generalize to become limbic seizures but rather spread to sensorimotor cortex to become manifest as motor seizures. Perirhinal cortical seizures also required larger kainic acid doses for provocation and were briefer.

Amygdala↗
PubMed2003

Treatment with vitamin B3 improves functional recovery and reduces GFAP expression following traumatic brain injury in rats.

Previous studies have shown that administration of vitamin B(3) (B(3)) in animal models of ischemia significantly reduced the size of infarction and improved functional recovery. The present study evaluated the effect of administration of B(3) on recovery of function following traumatic brain injury (TBI), incorporating the bilateral medial frontal cortex contusion injury model. Groups of rats were assigned to B(3) (500 mg/kg) or saline (1.0 ml/kg) treatment conditions and received contusion injuries or sham surgeries. Drug treatment was administered 15 min and 24 h following injury. Rats were examined on a variety of tests to measure sensorimotor performance (bilateral tactile adhesive removal), skilled forelimb use (staircase test), and cognitive ability (reference and working memory) in the Morris Water Maze. Administration of B(3) following injury significantly reduced the behavioral impairments observed on the bilateral tactile removal test, but not on skilled forelimb use. The acquisition of reference and working memory tests were also significantly improved compared to saline-treated rats. Examination of the brains revealed that administration of B(3) significantly reduced the size of the lesion compared to treatment with saline. In addition, examination of glial fibrillary acidic protein (GFAP) expression around the lesion revealed that B(3) significantly reduced the number of GFAP(+) astrocytes. These results indicate that B(3) administration significantly improved behavioral outcome following injury, reduced the size of the lesion, and reduced the expression of GFAP. The current findings suggest that B(3) may have therapeutic potential for the treatment of TBI.

Animals↗
PubMed2001

Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments.

Del22q11 syndrome is caused by heterozygous deletion of an approximately 3 Mb segment of chromosome 22q11.2. Children diagnosed with del22q11 syndrome commonly have learning difficulties, deficits of motor development, cognitive defects and attention deficit disorder. They also have a higher than normal risk for developing psychiatric disorders, mainly schizophrenia, schizoaffective disorder and bipolar disorder. Here, we show that mice that are heterozygously deleted for a subset of the genes that are deleted in patients have deficits in sensorimotor gating and learning and memory. The finding of sensorimotor gating deficits is particularly significant because patients with schizophrenia and schizotypal personality disorder show similar deficits. Thus, our deletion mouse models at least two major features of the del22q11-associated behavioral phenotype, and as such, represents an animal model of this complex behavioral phenotype. These findings not only open the way to pharmacological analyses that may lead to improved treatments, but also to the identification of gene/s that modulate these specific behaviors in humans.

Abnormalities, Multiple↗
PubMed2001

[Human performance against acute alcohol intoxication].

Analyzed were quantitative literary data on the effects of acute alcohol intoxication on performance. Reviewed were impacts of various doses of alcohol on the psychophysiological parameters and intricate sensorimotor functions of flying human operator. Alcohol was found to be unfavorable to the vestibular function and, therefore, predisposing to traffic and flight accidents. Hence, the alcohol CNS effects give rise to behavioral and psychophysiological disturbances. The psychophysiological disturbances are impaired concentration and dynamic visual function as a whole, deteriorated light differentiation ability and information perception, short-term amnesia, altered alertness and block, and associated lack of self-criticism and self-control.

Acute Disease↗
PubMed2003

Play preferences and behavior of preschool children with autistic spectrum disorder in the clinical environment.

The play of children with autistic spectrum disorder (ASD) is a valuable medium for assessment and intervention, and its analysis has the potential to aid diagnosis. This study investigated spontaneous play behavior and play object preferences for 24 preschool children with ASD in a typical occupational therapy clinical environment. Play behavior was rated and choice of play object noted at 10-second intervals from a 15-minute video recording of unstructured play. Statistical analyses indicated that play behavior was consistent with descriptions in the literature. In addition, the children demonstrated clear preferences for play objects in the form of popular characters (e.g., Thomas the Tank Engine) and those with sensorimotor properties. We propose that the inclusion of preferred play objects in a clinical environment may increase intrinsic motivation to play, and thereby enhance assessment and intervention.

Autistic Disorder↗
PubMed1991

Behavioral state-specific changes in human hippocampal theta activity.

Although there has been extensive examination of the behavioral and physiologic correlates of hippocampal theta activity in animals, the human literature consists of a single case study. We investigated the differential effects of four behavioral states on human hippocampal theta activity in 16 epilepsy surgery patients. Behavioral conditions included resting eyes closed (RC), resting eyes open (RO), eyes open with auditory word activation (AW), and eyes open with visuospatial activation (VS). Hippocampal theta activity decreased during both RO and VS compared to both RC and AW. There were reciprocal changes in delta activity. Comparisons of RO to VS and of RC to AW were nonsignificant. The results demonstrate state-specific changes in human hippocampal theta and are consistent with the animal literature that relates hippocampal theta to sensorimotor integration and forebrain volitional mechanisms.

Adolescent↗
PubMed1995

Dextromethorphan suppresses both formalin-induced nociceptive behavior and the formalin-induced increase in spinal cord c-fos mRNA.

The injection of dilute formalin results in a stereotyped nociceptive behavioral response. Administration of dextromethorphan (s.c.) but not saline, 30 min prior to intraplantar formalin injection prevents this nociceptive response in a dose-dependent manner. In addition, intraplantar formalin reliably induces c-fos mRNA in the ipsilateral spinal dorsal horn as assessed with quantitative solution hybridization at 30 min postinjection. No change in c-fos mRNA was detected in the contralateral spinal dorsal horn, nucleus raphe magnus, periaqueductal grey, medial thalamus, or sensorimotor cortex. Pretreatment with dextromethorphan at 60 mg/kg s.c., 30 min prior to formalin resulted in a suppression of c-fos induction, so that c-fos mRNA levels in the ipsilateral spinal dorsal horn of animals receiving dextromethorphan prior to formalin did not differ from controls. These data indicate that dextromethorphan suppresses formalin nociceptive behavior and one of the biochemical consequences of formalin nociception, i.e., induction of c-fos mRNA.

Animals↗
PubMed1997

Serial recording of somatosensory and myoelectric motor evoked potentials: role in assessing functional recovery after graded spinal cord injury in the rat.

Accurate functional outcome measures are essential in assessing therapeutic interventions after experimental spinal cord injury (SCI). We examined the hypothesis that serial recording of somatosensory (SSEP) and myoelectric motor evoked potentials (mMEPs) would provide complementary information to standard methods of behavioral analysis in a rat model of SCI and would allow objective discrimination of functional recovery in sensory and motor tracts. Clip compression injury of varying severity (sham, 23 g, 34 g, 56 g) and transections were performed at T1 in adult rats. SSEPs were recorded from the right sensorimotor cortex (SMC) after stimulation of the contralateral hind paw; mMEPs were recorded from the paraspinal, quadriceps, and the tibialis anterior muscles after anodal stimulation of the SMC. The inclined plane and Tarlov techniques were used to assess clinical neurological function. All outcome measures were assessed weekly prior to and up to 6 weeks following injury. Changes in clinical neurological function as assessed by the inclined plane and Tarlov methods varied with increasing injury severity (R = -0.72 and R = -0.73, respectively). SSEP latency was strongly correlated with injury severity (R = 0.92) and with clinical behavioral scores (R = -0.93 for inclined plane). The tibialis anterior mMEP correlated significantly, though weakly, with changes in inclined plane (R = 0.49) and Tarlov scores (R = 0.41). Although the mMEPs were sensitive to the presence of SCI, these recordings did not discriminate between severities of injury. We conclude that serial recording of SSEPs but not myoelectric MEPs correlates closely with the extent and temporal course of clinical neurological recovery after graded SCI in the rat.

Animals↗
PubMed2004

Bimanual coordination: neuromagnetic and behavioral data.

It has been suggested that bimanual coordination is associated with stronger activation of the left motor cortex in right-handers. The aim of the present study was to investigate whether left motor cortex dominance constitutes a fundamental feature of bimanual coordination. We investigated neuromagnetic responses while subjects performed a bimanual tapping task using a 122-channel whole-head neuromagnetometer. Three neuromagnetic sources localized in the primary sensorimotor cortex of each hemisphere were found. Sources represent neuromagnetic correlates of the motor command and of somatosensory feedback. Since we found no differences of amplitudes or latencies of corresponding sources of both hemispheres, our data suggest that dominance of the left motor cortex is not a fundamental characteristic for bimanual coordination.

Adult↗
PubMed1989

Neuroethological evaluation of audiogenic seizures in hemidetelencephalated rats.

Wistar-derived male rats were tested for audiogenic seizure (AS) susceptibility, and classified into sensitive (S) and resistant (R) groups. Rats from group R underwent unilateral ablation of the telencephalon, or were detelencephalated (HD), or sham-lesioned, and were tested for audiogenic susceptibility one month and one year after surgery. It was found that previously AS-resistant, HD-operated animals developed generalized tonic-clonic convulsions upon high intensity (110.8 dB) acoustic stimulation, with higher severity and shorter latencies than the susceptible, non-operated control animals. Sham-lesioned R animals maintained their previous resistance to AS. HD-lesioned R animals also presented asymmetric motor patterns, such as gyrating and barrel-rolling behavior, always oriented towards the side contralateral to the lesion. HD-lesioned S animals presented an increase in the severity of seizures, as well as a shortening of the latencies of the running (procursive) and convulsive phases of the seizures. This effect was more marked one year after surgery. Contralateral barrel-rolling behavior was also observed in these animals. The fact that seizure severity increases and latency decreases with time after lesion seems to indicate a role for denervation hypersensitivity and other cerebral plasticity phenomena in explaining the effects of HD lesions on AS. The fundamental neural structures involved appear to be those related to sensorimotor coordinating systems (substantia nigra/pontine-mesencephalic reticular formation and substantia nigra/superior colliculus), the acoustic pathways (inferior colliculus) and their projections to the superior colliculus and reticular formation.

Acoustic Stimulation↗